In general, the sterilization of medical products depends upon the ability of the process to kill pathogenic microorganisms. The application of radiation to sterilize medical products is widely used throughout the world and recognized as a safe, effective form of sterilization. The first commercial application of electron beam sterilization processing for medical devices was developed by Ethicon Inc., a subsidiary of Johnson and Johnson in 1956. In the early 1960s the use of gamma rays from Cobalt-60 for the sterilization of disposable medical devices was being developed in the United Kingdom. Because of the poor reliability of the early electron beam systems, the radiation sterilization of medical products was dominated by Cobalt-60 (gamma) irradiators, which had no similar reliability issues.
With the advent of national laboratories devoted to high-energy physics research, a major effort was put into improving the reliability and performance of critical accelerator components. By the 1970s, industry's involvement in developing radiographic and oncology machines further enhanced the durability and reliability of electron accelerators. This improvement of component performance—along with the integration of computerized controls—encouraged reevaluation of the commercial possibilities of the technology. Soon thereafter, interest in high-energy (>300 keV) E-beam based sterilization was rapidly growing.
Perhaps the largest industrial application of radiation is the modification of polymers. Radiation is used to polymerize and cure monomers into polymers, to cross-link polymers, and to graft different types of monomers onto polymer molecules to form new materials with special properties. Radiation is also used for the intentional degradation of polymers and for tailoring of molecular weight distributions to serve special industrial and commercial purposes. This industrial application of radiation is dominated by low energy (<300 keV) electron beam systems.
In 1999, use of a low-energy (<300 KeV) E-beam system in sterilization of medical devices was described in U.S. patent application Ser. No. 09/294,964, filed Apr. 20, 1999, now U.S. Pat. No. 7,264,771, assigned to the assignee of the present application, Baxter International, the relevant disclosure of which is hereby incorporated by reference. E-beam sterilization unit size and cost were two big factors feeding the move toward low-energy sterilization systems. Depth of the sterilizing radiation penetration became the trade-off. Where high-energy systems may achieve penetration depths of over a meter, low-energy beams are limited to penetration depths of as low as only a few microns.
The significantly reduced radiation penetration of low-energy electron beams used for medical device sterilization raised the issue of sterility validation as a processing concern. The FDA requires that “all processes used to produce medical devices be validated” (21 C.F.R. §820.752), including E-beam sterilization. The goal of such validation is to determine the minimum exposure dose that can be used to meet a desired sterility assurance level and allow “dosimetric release,” which is the determination that a product is sterile based on physical irradiation process data rather than actual sterility testing.
Therefore, validation must begin with the selection of a sterility assurance level (SAL), a measure of the probability that one unit in a batch will remain non-sterile after being exposed to a specific sterilant. For example, an SAL of 10−3 means that one device in a thousand may be non-sterile. Selecting the proper SAL occurs during a dose-setting phase of radiation sterilization validation. In many cases, the intended use of the device will dictate the need for a particular SAL. The commonly accepted SAL for invasive medical devices is 10−6. However, some European countries only recognize 10−6 SAL for a claim of “sterile.” In such cases, the country of intended use will dictate the SAL as much as the device's intended use.
Although both gamma and ethylene oxide-gas sterilization are validated, effective and readily available technologies, the increased focus on E-beam can be ascribed to its having the shortest process cycle of any currently recognized sterilization method. In both high- and low-energy E-beam processing, the products are scanned for seconds, with the bulk of the processing time devoted to transporting the products into and out of a shielded booth. With the use of established and recognized dosimetric release procedures, a product under going high-energy E-beam sterilization can be released from quarantine as sterile within 30 minutes. The prior art, however, has not sufficiently developed a method for validation and routine monitoring of low-energy E-beam sterilization.
As a solution to this problem, the present invention has been developed which provides an apparatus for use in the validation of low-energy electron beam sterilization systems. Furthermore, the invention provides a method that cost-effectively and reliably provides for the routine dosimetric monitoring of the sterilization process for low-energy electron beam sterilization systems.